HIV infection and antiretroviral therapy lead to unfolded protein response activation

Virology Journal

Aguinaldo R. Pinto³  Dumith Chequer Bou-Habib²  Maristela M. Camargo⁴  Luiz G. E. Ferreira⁵  Andrea Petry¹  Pedro L. C. Ferreira²  Mariana Borsa³ 

[1] Centro de Hematologia e Hemoterapia de Santa Catarina, Florianópolis, SC, Brazil;Laboratório de Pesquisas sobre o Timo, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil;Laboratório de Imunologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil;Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil;Hospital Regional Homero de Miranda Gomes, São José, SC, Brazil

关键词: Cell stress;    Antiretroviral therapy;    Endoplasmic reticulum stress;    UPR pathway;    Aids;    HIV;   

Others  :  1224936
DOI  :  10.1186/s12985-015-0298-0

 received in 2015-01-26, accepted in 2015-04-09,  发布年份 2015

【 摘 要 】

Background

The unfolded protein response (UPR) is one of the pathways triggered to ensure quality control of the proteins assembled in the endoplasmic reticulum (ER) when cell homeostasis is compromised. This mechanism is primarily composed of three transmembrane proteins serving as stress sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1). These three proteins’ synergic action elicits translation and transcriptional downstream pathways, leading to less protein production and activating genes that encode important proteins in folding processes, including chaperones. Previous reports showed that viruses have evolved mechanisms to curtail or customize this UPR signaling for their own benefit. However, HIV infection’s effect on the UPR has scarcely been investigated.

Methods

This work investigated UPR modulation by HIV infection by assessing UPR-related protein expression under in vitro and in vivo conditions via Western blotting. Antiretroviral (ARV) drugs’ influence on this stress response was also considered.

Results

In in vitro and in vivo analyses, our results confirm that HIV infection activates stress-response components and that ARV therapy contributes to changes in the UPR’s activation profile.

Conclusions

This is the first report showing UPR-related protein expression in HIV target cells derived directly from HIV-infected patients receiving different ARV therapies. Thus, two mechanisms may occur simultaneously: interference by HIV itself and the ARV drugs’ pharmacological effects as UPR activators. New evidence of how HIV modulates the UPR to enhance its own replication and secure infection success is also presented.

【 授权许可】

   
2015 Borsa et al.

【 图 表 】

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